Over the last quarter of a century, scientists have released hundreds of studies suggesting a small set of particular genes or gene variants, playing a major role in increasing susceptibility to depression. Such papers were hoping that clinicians could quickly use genetic testing to simply identify the risks and drug companies could develop drugs to counteract some genetically engineered sinners.
However, a new University of Colorado Boulder study, which evaluated genetic and study data from 620,000 individuals, found that the 1
The previous studies were false or false positives – and the scientific community should leave the so-called "candidate gene hypotheses", the authors conclude.
"This study confirms that efforts to find a single gene or a handful of genes that determine depression are doomed to failure," said lead author Richard Border, a graduate student and researcher at the Department of Behavioral Genetics.
adds senior author Matthew Keller, Associate Professor of Psychology and Neuroscience:
"We do not say that depression is not hereditary at all. That is what we say depression is influenced by many many variants, and each one has each for a minimal effect. "
For the e-study published in the American Journal of Psychiatry the authors looked at 18 genes that have appeared at least 10 times in depression-focused studies. Among them, a gene called SLC6A4 was involved in the transport of the neurochemical serotonin. Research goes back 20 years suggesting that people with a certain "short" version of the gene have a significantly greater risk of depression, especially when exposed to early life trauma.
The researchers also looked at genes involved in the production of brain-derived neurotrophic factor (BDNF) a protein involved in nerve formation and neurotransmitter dopamine.
Using genetic and study data collected from individuals via UK Biobank, 23andMe and Psychiatric Genomics Consortium, they set out to see if any of the genes or gene variants were associated with depression either alone or in combination with an environmental factor such as childhood trauma or socio-economic diversity.
The study is the largest and most comprehensive study to date for historical depression candidate genes.
"We found out that these candidate genes as a set are no more related to depression than any random gene out there," Keller said. "The results, even for us, were a bit amazing."
Keller notes that in genetics, scientists have known for years that candidate gene hypotheses were flawed. But hopeful scientists in other fields, including psychology, have continued to publish studies – often based on smaller sizes – that have kept the idea of a small set of "depression genes" alive.
"It's like in the Emporer Wears No clothes. & # 39; There's just nothing there," Keller said. "I hope this is the last stitch in the coffin for those kinds of studies."
He and Border emphasize that their results do not mean that research into the genetic support of depression should cease. Instead, they say it should recognize that the genetic architecture of depression is more complicated than once believed.
By understanding the thousands of genes associated with the disease and what they do, researchers can ultimately provide more precise "polygenic scores" to predict risk and still potentially develop drugs designed to counteract this risk. , they said.
Meanwhile, Border says that consumers should be cautious about claiming that individual genes have great effects on complex behavior.
While the risk of some medical conditions, such as breast cancer and Alzheimer's disease, has been clearly linked to individual genes, it is not as simple with traits as depression.
"Every time someone claims to have identified the gene that & # 39; causes a complex trait, is a time to be skeptical," said the border.
New knowledge could help predict and prevent depression
Richard Border et al., No support for historical candidate gene or candidate gene-to-interaction hypotheses for major depression over several large specimens, American Journal of Psychiatry (2019). DOI: 10.1176 / appi.ajp.2018.18070881
Study debunks depression genes & # 39; hypotheses (2019, April 3)
April 3, 2019
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